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Maria‐Pau GinebraBiomaterials, Biomechanics and Tissue Engineering GroupDepartment of Materials Science and MetallurgyTechnical University of Catalonia.BarcelonaTech (UPC)Barcelona, [email protected]
Calcium Phosphate Ceramics
Madrid, 17‐19 June 2015
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Outline
Synthetic bone grafts: concept and applications
Why Calcium phosphates?
Calcium phosphate sources: natural vs synthetic
High‐T vs low‐T calcium phosphates
Porosity in Calcium Phosphates
Biological performance of Calcium Phosphates: resorption, bioactivity and osteoinduction
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Bone Grafting procedures
2 million bone grafting proceduresworldwide every year
≈ 1 million in EuropeGreenwald AS et al. J Bone Joint Surg Am. 2001;83‐A, suppl 2, part 2:98‐103.
Allografts Autografts Xenografts
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Applications of synthetic bone grafts
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Applications of synthetic bone grafts
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Treatment of bone tumors is one of the clinical fields were bone grafts
are required
Maxillofacial reconstruction(cleft lip and palate)
Applications of synthetic bone grafts
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30% 70%
95%
2%
Hydroxyapatite (95%)(Biological apatite)
Why Calcium Phosphates?
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Why Calcium Phosphates?
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“Form follows function” Louis Sullivan (1896)
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Mechanical: support and protection – strength and toughness
Metabolic: Ion reservoir / Protein and growth factor regulation
Autorepair
Bone Dental Enamel
Mechanical: to tear and chewfood ‐ hardness, resistance to abrasion
Resistance to acidic dissolution
Partial re‐mineralization
Hard tissue functions
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Calcium Phosphates:
Hydroxyapatite β‐Tricalcium Phosphate Biphasic Calcium Phosphates (HA/β‐TCP)
Conventional Calcium Phosphates
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Granules (0.1-5 mm) Block
Cement Putty
M. Bohner, Materials today(2010) 13:24-30
Shapes and Forms
Coating
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Natural• Bovine bone
• Coral
Synthetic• High temperature
• Low temperature
Origin of commercial CaP
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Coralline Hydroxyapatite
• Hydrothermal conversion (260 ºC, 15,000 psi) of coral (mostly CaCO3, calcite form) in the presence of ammonium phosphate to hydroxyapatite (Interpore™ and Pro‐Osteon™ manufactured by Interpore International, Inc, Irvine, CA)
4CaCO3 + 6(NH4)2HPO4 → Ca10(PO4)6(OH)2 + H2O+CO2
• F, Sr, and CO3 present in the coral become incorporated in the resultinghydroxyapatite. Other ions (Mg) become incorporated in the minor ‐TCP componentthat forms after hydrothermal conversion.
CaP of natural origin
Trabecular bovinebone-derivedhydroxyapatite(Endobon™), Coralline
hydroxyapatite(Interpore ™).
R.Z. LeGeros, Clin. Orthop. Rel. Res. 395 (2002): 81–98
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Bovine‐bone Derived Apatites
2 types, depending on the method of preparation:
(1) unsintered (Bio‐Oss™, by Geistlich Biomaterials, Geistlich, Switzerland)
(3) sintered (Osteograf‐N™ by CeraMed Co Denver, CO and Endobon™ by Merck Co, Darmstadt, Germany).
• The unsintered bone mineral consists of small crystals of bone apatite(carbonatehydroxyapatite) and other trace elements originally present in bone, whereasthe sintered bone mineral consists of much larger apatite crystals without CO3 whensintered above 1000 ºC.
• Safety concerns after mad cow disease (Creutzfeldt–Jakob disease ): bovine‐derived graft biomaterials may carry a risk of prion transmission to patients.
CaP of natural origin
Wenz B, Oesch B, Horst M. Biomaterials. 22 (2001):1599-606.Kim Y, Nowzari H, Rich SK.Clin Implant Dent Relat Res. 15 (2013):645-53.
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Synthetic CaPs
High TemperatureSintered ceramicsCoatings (plasma spray)
Low Temperature: Biomimetic CaPsCalcium phosphate cementsBiomimetic coatingsCaP Nanoparticles
Synthetic CaP
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High Temperature CaPs: sintered ceramics
Precursor powders
Hydroxyapatite 1050-1300 Cβ-TCP 1000-1100 C
Mixing Compactation
Furnace
High-T Sintered ceramic
High Temperature CaPs: Sintered ceramics
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High Temperature CaPs: sintered ceramicsHigh Temperature CaPs: Sintered ceramics
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LeGeros, R.Z. Chem. Rev. 2008, 108, 4742–4753
High Temperature CaPs: sintered ceramicsHigh Temperature CaPs: Sintered ceramics
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Synthetic CaPs
High TemperatureSintered ceramicsCoatings (plasma spray)
Low Temperature: Biomimetic CaPsCalcium phosphate cementsBiomimetic coatingsCaP Nanoparticles
High T CaP ceramics vs low T biomimetic CaP
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Low-T CaPs: Calcium Phosphate Cements
PlasticpastePlasticpaste
RigidpasteRigidpaste
Solid body
Powder Liquid
Setting
Hardening
Dissolution
+
Precipitationat
physiologicaltemperature
Dissolution
+
Precipitationat
physiologicaltemperature
Low T setting reaction
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M.P. Ginebra et al., Adv Drug Del Rev (2012)
Micro & nanoporosity
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High T CaP ceramics vs low T biomimetic CaP
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Micro/nanoporosity: ‐ Increased bioactivity‐ Effect on protein adsorption, and celladhesion/proliferation‐ Permeability: nutrient and cell metabolic wastesubstances diffusion.
Macroporosity: cell/tissue colonisation. ‐migration, proliferation and differentiation of osteoblast progenitor cells.‐ angiogenesis.Size > decens/hundreds mNeed of interconnected porosity
Bone regenerationThe role of porosity
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3 ‐Ca3(PO4)2 + H2O → Ca9(HPO4)(PO4)5(OH)
Montufar et el. Acta Biomater 6 (2010) 876–885
Macroporous CaPs: Injectable Calcium phosphate foams
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Porous ceramics: injectable HA foams
Montufar et el. Acta Biomater 6 (2010) 876–885
Macroporous CaPs: Injectable Calcium phosphate foams
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Ceramic ink• Non‐reactive suspension: Printing + Sintering• Suspension of reactive ceramic particles Self‐setting
scaffolds
Tomsia et al (2007)
Macroporous CaPs: 3D printing strategies
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Self‐setting Ceramic Ink: Gelatin‐αTCP
‐ Gelatine gellation: initialconsolidation of the scaffold
‐ Subsequently: αTCP hydrolysis to Hydroxyapatite
Macroporous CaPs: 3D printing strategies
Y. Maazouz, E. B. Montufar, J. Guillem-Marti, I. Fleps, C. Ohman, C. Persson, M. P. GinebraJ. Mater. Chem. B, 2014, 2, 5378–5386
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Biological performance of CaP
• Resorption
• Bioactivity / Osteoconduction
• Osteoinduction
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Biological performance of CaP: Resorption
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Chemical dissolution
Plaster of Paris (CSH), Gypsum (CSD),
Dicalcium phosphate dihydrate (DCPD)
Cell-mediatedosteoclasts, macrophages…
Precipitated Hydroxyapatite *-Tricalcium phosphate
Biphasic calcium phosphates
Passive resorption Active resorption
Biological performance of CaP: Resorption
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Chemical dissolution
Plaster of Paris (CSH), Gypsum (CSD),
Dicalcium phosphate dihydrate (DCPD)
Cell-mediatedosteoclasts, macrophages…
Precipitated Hydroxyapatite *-Tricalcium phosphate
Biphasic calcium phosphates
Passive resorption Active resorption
Reactivity: Stoichiometry Cristallinity Specific surface
area Porosity
Sintered HA
Non resorbable
HA Biological HA
Resorbable
Biological performance of CaP: Resorption
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D.G. Castner, B.D. Ratner / Surface Science 500 (2002) 28–60
Biological performance of CaP: Bioactivity
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Bioactive glasses and glassceramics
Calcium phosphates
AluminaZircona
Bioceramics
Bioinert Bioactive
+/‐ biodegradable
Biological performance of CaP: Bioactivity
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S. del Valle, M.P. Ginebra et al. J Mater Sci: Mater Med (2007) 18:353–361
Biological performance of CaP: Bioactivity
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La osteoinduction: differentiation of mesenchymal stem cells (pluripotent)to the osteoblastic phenotype.
Biological performance of CaP: Osteoinduction
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Two strategies to trigger osteoinduction:
1. Incorporation of bone morphogenetic proteins (BMPs) in thebiomaterials.
2. Designing intrinsically osteoinductive biomaterials
Biological performance of CaP: Osteoinduction
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M. C. Barradas, H. Yuan, C. A. Van Blitterswijk, P. Habibovic, Eur. Cells Mater. 21 (2011), 407–29
Biological performance of CaP: Osteoinduction
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Summary
• CaP have unique properties as synthetic bone grafts
• CaP can be obtained either from natural sources of by synthetic processes either at high‐T or low‐T
• The biological performance of CaP (resorption, bioactivity and osteoinduction) depends not only on their composition but also on their porosity and textural properties. Their control can allow actively directing the material‐cell/tissue interaction.
• CaP processing is compatible with promising strategies for the fabrication of macroporous CaP scaffolds for tissue engineering and bone regeneration.
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PostDoc fellows
Montserrat EspanolCristina CanalGiuseppe Scionti
PhD students
Yassine MaazouzDavid PastorinoAnna DiezZhitong ZhaoKanupriya KhuranaAlbert Barba
Acknowledgements
Funding bodies
